Medical Neuroscience explores the functional organization and neurophysiology of the human central nervous system, while providing a neurobiological framework for understanding human behavior. In this course, you will discover the organization of the neural systems in the brain and spinal cord that mediate sensation, motivate bodily action, and integrate sensorimotor signals with memory, emotion and related faculties of cognition. The overall goal of this course is to provide the foundation for understanding the impairments of sensation, action and cognition that accompany injury, disease or dysfunction in the central nervous system. The course will build upon knowledge acquired through prior studies of cell and molecular biology, general physiology and human anatomy, as we focus primarily on the central nervous system.
This online course is designed to include all of the core concepts in neurophysiology and clinical neuroanatomy that would be presented in most first-year neuroscience courses in schools of medicine. However, there are some topics (e.g., biological psychiatry) and several learning experiences (e.g., hands-on brain dissection) that we provide in the corresponding course offered in the Duke University School of Medicine on campus that we are not attempting to reproduce in Medical Neuroscience online. Nevertheless, our aim is to faithfully present in scope and rigor a medical school caliber course experience.
This course comprises six units of content organized into 12 weeks, with an additional week for a comprehensive final exam:
- Unit 1 Neuroanatomy (weeks 1-2). This unit covers the surface anatomy of the human brain, its internal structure, and the overall organization of sensory and motor systems in the brainstem and spinal cord.
- Unit 2 Neural signaling (weeks 3-4). This unit addresses the fundamental mechanisms of neuronal excitability, signal generation and propagation, synaptic transmission, post synaptic mechanisms of signal integration, and neural plasticity.
- Unit 3 Sensory systems (weeks 5-7). Here, you will learn the overall organization and function of the sensory systems that contribute to our sense of self relative to the world around us: somatic sensory systems, proprioception, vision, audition, and balance senses.
- Unit 4 Motor systems (weeks 8-9). In this unit, we will examine the organization and function of the brain and spinal mechanisms that govern bodily movement.
- Unit 5 Brain Development (week 10). Next, we turn our attention to the neurobiological mechanisms for building the nervous system in embryonic development and in early postnatal life; we will also consider how the brain changes across the lifespan.
- Unit 6 Cognition (weeks 11-12). The course concludes with a survey of the association systems of the cerebral hemispheres, with an emphasis on cortical networks that integrate perception, memory and emotion in organizing behavior and planning for the future; we will also consider brain systems for maintaining homeostasis and regulating brain state.

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Movement and Motor Control: Lower and Upper Motor Neurons

We come now to another pivot in Medical Neuroscience where our focus shifts from sensation to action. Or to borrow a phrase made famous by C.S. Sherrington more than a century ago (the title of his classic text), we will now consider the “integrative action of the nervous system”. We will do so in this module by learning the basic mechanisms by which neural circuits in the brain and spinal cord motivate bodily movement.

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Leonard E. White, Ph.D.

Associate ProfessorDepartment of Neurology, Department of Neurobiology, Duke University School of Medicine; Department of Psychology & Neuroscience, Trinity College of Arts & Sciences; Director of Education, Duke Institute for Brain Sciences; Duke University

This figure shows us Nissl-stained section through the lumbar level of the

human spinal cord. And if you've not yet taken the time to

see my overview of the internal anatomy of the spinal cord, this might be a good

time to pause and have a look at that particular tutorial.

I think that will help you out, with some aspects of where we're going to go over

the next few minutes. if you have seen that, great.

Let's go ahead and move on. So I won't go through the detail of the

organization of the gray matter and the white matter of the spinal cord.

Rather I'll draw your attention to the ventral horn, and to a set of columns of

neurons that we call laminae seven through nine.

And that's these columns that contain our lower motor neurons, and even at this

lower magnification, I think you can see that in this region of the ventral horn,

we have these large neurons that are present.

And, of course, I'd like to show you those in more detail.

And so, just to give you a higher magnification view of what they actually

look like. here we see some lower motor neurons, and

they have a very characteristic morphology to them.

They're, first of all, are very large cells.

They have, sort of, a multi-polar shape, this is a Nissl stain, so we're not

seeing all of the dendrites that are extending off in various directions.

but what we see is a cytoplasm that's just full of darkly staining Nissl

substance. Which is indictive of rough endoplasmic

reticulum in the production of proteins. We see quite a large nucleus and a very

prominent, and single nucleolus near the center of that nucleus.

So this is the characteristic appearance of a typical motor neuron.

Here we have another one. The plane of focus is just a little bit

off the nucleolus but I think you can see that, nuclear membrane there and then the

nucleolus here in the center. Well that's what the motor neurons

actually look like. how are they distributed in the ventral

horn, is the topic that I'd like to spend just a few minutes discussing with you

next. Now you already know that along the long

axis of the spinal cord, there are two regions in which the diameter of the

spinal chord is significantly enlarged. There is the cervical enlargement and the

lumbosacral enlargement. And these enlargements reflect the

additional circuitry and the additional numbers of neurons, that are in those

segments of the spinal chord that serve the upper extremities and the lower

extremities. Well that's what's going on along the

length of the spinal cord as we look at the gross organization of the structure.

If we look at a finer scale, what we see are that within the cervical enlargement,

or within the lumbosacral enlargement. The neurons that supply a given muscle

are also extended over some distance across multiple segments of the spinal

cord. And we see in this figure the result of

an experiment that demonstrates this point.

So what was done in this experiment is that the gastrocnemius muscle in an

animal model was injected with a dye substance.

That is taken up at the neuromuscular junction by the axons of the alpha motor

neurons that innervate that muscle. And then this dye is transported back to

their cell bodies. And then the experimenters can look into

the spinal chord in histological sections, and plot the location of the

cells that were labeled by injecting the specific muscle.

Well, the same kind of experiment was also done for the soleus muscle on the

opposite side of the body. And as a result, what we see, is a column

of cells on one side of the spinal cord that reflects the distribution of motor

neurons that supply the gastrocnemius. And on the other side of the spinal cord,

are the labeled motor neurons that innervate the soleus muscle.

And the point here is that for each muscle.

There is column of cells. Perhaps not unlike this writing device

that I'm holding. That is distributed across multiple

segments of the spinal cord. And when we look at their positions, we

find that they're not overlapping necessarily.

There may be some order to their distribution in the medial to lateral

aspect of the ventral horn. In fact, this is a very important

principle of ventral horn organization that I want to stress for you.

If we look at the arrangement of these columns of motor neurons that innervate

specific muscles. What we see is a beautiful and, and

hopefully memorable, somatopic organization.

Again, I'll use this word somatotopy that we talked about when we considered the

somatic sensory system, to refer to the mapping of the body.

So we see a kind of somatotopy now in the organization of our lower motor neurons,

in the ventral horn of the spinal chord. What we see are neurons that are present

in the medial part of the ventral horn, are supplying muscles that are found in

the more proximal portions of the extremities.

Or perhaps in the trunk muscles themselves, if we're talking about the

thoracic spinal cord. Whereas as we get to progressively more

lateral positions in the vental horn, we move from proximal to distal, such that

the muscles that govern the movements of the distal extremities.

Which is where so much of the skill is expressed especially via the activities

of our arms and hands. These motor neurons are found out here in

lateral part of the ventral horn. So it's very important to recognize this

menial to lateral somatotopic organization in the ventral horn.

Because that will provide an important framework for understanding the

descending projections from upper motor neurons.

We'll recognize that the descending projections that reside in this ventral,

or interior white matter of the spinal chord, are mainly supplying the medial

aspects of the ventral horn. Whereas the major fiber bundle that sits

out there in the lateral column of the spinal cord is the lateral cortical

spinal tract. And this system is mainly concerned with

supplying the lateral aspects of the ventrical horn.

So getting back to our general orginization framework then, I hope you

can recognize that what's going on in this ventral and anterior white matter.

Is mostly concerned with setting the stage for skill behavior in adjusting

posture, setting gain, and otherwise facilitating what we do with our distal

extremities. And what's happening out here in the

lateral part of the spinal cord is mainly an expression of skilled behavior.

Now I won't spend much time right now reviewing for you again the organiziton

of the motor elements of our cranial nerve nuclei.

Rather, I'll just refer you back to the tutorial regarding the internal

organization of the brain stem, and the organization of the cranial nerves and

their nuclei. And there, what we talked about was the

outflow from somatic motor and branchial motor nuclei.

That are concerned with moving muscles derived from somites or from the

pharyngeal arches, respectively. And these motor nuclei are found in each

of the three major divisions of our brain stem.

In the mid brain, we have the oculomotor nucleus and the trochlear nucleus, And

then in the pons we have the abducens nucleus.

These three semantic motor nuclei govern the movements of the eyes in the orbit.

And then down in the upper part in the medulla, we have the hypoglossal nucleus,

that is concerned with the movements of the tongue.

And with respect to governing those muscles derived from the pharyngeal

arches in the pons, we have the trigeminal motor nucleus that innervates

the muscles of chewing. We have the facial motor nucleus, that

supplies the muscles of the face that are involved in facial expressions of

emotion. And then, further down in the brainstem,

in the medulla, and in the upper cervical segments of the spinal cord, we find

first the nucleus ambiguous, which is governing the muscles of the pharynx and

the larynx. And, in the upper cervical cord, the

spinal accessory nucleus, which is interveining the pharyngeal arch derived

muscles that turn the head and shrug the shoulders.

Well, I do want to at least show you what these motor neurons look like, just to

illustrate the point that, in the cranial nerve motor nuclei.

We have alpha motor neurons, very much like the motor neurons, that we find in

the ventral horn of the spinal cord. This is a detailed look at one of our

branchiomeric motor nuclei, the trigeminal motor nucleus.

And here is roughly the boundaries of this nucleus, and so this is where we

would find our columns of cells that are providing innervation to the muscles of

mastication. Those muscles that we use when we chew

and consume food. And what we see are beautiful

demonstrations of alpha motor neurons that have all the same histological

features as what we saw in the ventral horn of the spinal cord.

And lastly what I'd like to do in this tutorial is to talk about the motor unit.

And describe for you just some of the physiological features of

musculo-skeletal behavior, that we want to keep in mind as we move into a

deeper discussion of how the nervous system controls movement.

So, the alpha-motor neuron at the spinal chord is what we've been talking about

and here's an illustration of an alpha-motor neuron, sitting in the

ventral horn of the spinal chord. And, it sends it's axons out through the

ventral root into a spinal nerve and then as that spinal nerve supplies a muscle,

this axon will divide into several branches.

And these branches will then go on to supply innervation to a set of muscle

fibers within a muscle. And these muscles fibers tend to be

broadly distributed within that muscle. So the motor unit is defined as the

single alpha motor neuron plus the muscle fibers that it intervates.

That's the motor unit. Now a single motor unit can be classified

not just atomically, but also physiologically.

There is coordination between the neuron and the muscle fibers for the functions

that that motor unit must perform. So from a physiological perspective there

are biochemical and even neuro specializations.

That allow these three types of motor units to contribute to physiological

activities of entire muscles in distinct ways.

First we have a type of motor unit that we classify as being slow.

This is a motor unit that doesn't generate a whole lot of force, and it

does so fairly slowly. so what we're looking at is the response

to a single action potential, that is applied to the axon that innervates a

particular type, a particular set of muscle fibers.

Now if that action potential arrives at a different collection of muscle fibers, we

might see a more significant amount of force generated, and it might happen more

quickly. this we call the fast fatigue resistant

motor unit. And then, if we apply that action

potential to yet a third motor axon. We might find a much larger amount of

force generated very rapidly, by the contraction of a muscle fiber that

happens to be innervated by that axon. If, so, that kind of physiological

profile, we would know that we're dealing with a fast fatigable motor unit.

Now, if we applied a series of pulses, not just an individual shock but a train

of pulses we might find something that looks quite similar, except now we would

see evidence of sustained response. And so with the activation of the slow

motor units, notice how each individual contraction takes some time.

And we build up our steady state level of forced production, and can substain that

over the duration of the brief train of pulses that is applied in this

experiment. The fast fatigue resistant motor unit

does considerably better with force production as can be seen, and notice

that it takes, much less time to generate that force.

And I want you to notice what happens when we get to our fast fatigable motor

unit. Of course, this is going to give us the,

greatest amount of force generated, with activation of the axon that supplies this

set of muscle fibers, and the force that's generated happens very rapidly.

But notice that even over the duration of a second or so of stimulation, there is

some decrement. And the amount of force that can be

sustained over time. And so, it's for this reason, that we

talk about the fatigue profile of these motor units.

So that of course, can be seen if we extend our stimulation, not just over a

second or so, but over many minutes. And what we find is that our slow motor

units, are those that can maintain their maximum amount of force production for a

very long period of time. Not indefinitely of course, but for a

long period of time. So, again, the amount of force that's

generated is small, and the speed at which that force is generated at a